ABSTRACT
There are varying definitions of women at high risk of breast cancer across different institutions, and there are reports suggesting that the breast cancer risk assessment tools have not been well integrated into clinical practice. In this study, we tried to investigate the perceived importance of different breast cancer risk factors by physicians in China. A cross-sectional survey involving 386 anonymous physicians was conducted using a 20-item, 5-point Likert scale questionnaire. The Kruskal-Wallis test and post-hoc pairwise comparisons were used to compare the differences in response. Most of the respondents were either breast surgeons/specialists (n=161; 41.7%) or medical oncologists (n=151; 39.1%), and the results showed that the breast cancer risk factors were not perceived as equally important. The weighting of each risk factor also varied depending on the physician's medical specialty, location of practice, and the number of years of clinical experience. This study provides a more updated insight into the perceptions of physicians in China toward the breast cancer risk factors, as well as underlines the potential improvements in breast cancer risk assessment strategies that can be done.
Subject(s)
Breast Neoplasms , Early Detection of Cancer/psychology , Oncologists/psychology , Physicians/psychology , Surgeons/psychology , Adult , Attitude of Health Personnel , China , Cross-Sectional Studies , Female , Humans , Middle Aged , Practice Patterns, Physicians'/statistics & numerical data , Surveys and QuestionnairesABSTRACT
PURPOSE: Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment. MATERIALS AND METHODS: We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model. RESULTS: Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060. CONCLUSION: RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC.
Subject(s)
Biomarkers, Tumor/metabolism , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-met/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Triple Negative Breast Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Animals , Apoptosis , Biomarkers, Tumor/genetics , Cell Movement , Cell Proliferation , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Mice , Mice, Nude , Middle Aged , Prognosis , Proto-Oncogene Mas , Proto-Oncogene Proteins c-met/genetics , Receptor Protein-Tyrosine Kinases/genetics , Survival Rate , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
Exosomes and long non-coding RNAs (lncRNAs) are emerging as important elements contributing to a more comprehensive understanding of cancer development and progression. The discovery of lncRNAs in exosomes further indicates their bona fide biological functional roles in cancer development and drug resistance. In this review, we describe the biogenesis of exosomes and summarize the function of exosomal lncRNAs in the field of cancer research. These findings strikingly advance current knowledge of exosomal lncRNAs and suggest that they may be promising diagnostic biomarkers and therapeutic targets for cancer.
Subject(s)
Exosomes/physiology , Neoplasms/genetics , RNA, Long Noncoding/physiology , Humans , Neoplasms/diagnosis , Neoplasms/therapyABSTRACT
Cancer remains a serious healthcare problem despite significant improvements in early detection and treatment approaches in the past few decades. Novel biomarkers for diagnosis and therapeutic strategies are urgently needed. In recent years, long noncoding RNAs (lncRNAs) have been reported to be aberrantly expressed in tumors and show crosstalk with key cancer-related signaling pathways. In this review, we summarized the current progress of research on cytoplasmic lncRNAs and their roles in regulating cancer signaling and tumor progression, further characterization of which may lead to effective approaches for cancer prevention and therapy.
Subject(s)
Neoplasms/genetics , RNA, Long Noncoding/genetics , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cytoplasm/genetics , Cytoplasm/metabolism , Hippo Signaling Pathway , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Neoplasms/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA, Long Noncoding/metabolism , Signal Transduction/geneticsABSTRACT
The purpose of this study was to elucidate the potential role of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) in gemcitabine (Gem)-induced autophagy and apoptosis in breast cancer cells. MDA-MB-231 cells were treated with short hairpin RNA (shRNA) to knockdown Linc-ROR expression in the presence of Gem. Gem treatment alone decreased cell survival and increased both apoptosis and autophagy. Gem treatment also increased the expression of LC3-II, Beclin 1, NOTCH1 and Bcl-2, but decreased expression of p62 and p53. Untreated MDA-MB-231 cell lines strongly expressed linc-ROR, but linc-ROR knockdown decreased cell viability and expression of p62 and p53 while increasing apoptosis. Linc-ROR knockdown also increased LC3-II/ß-actin, Beclin 1, NOTCH1, and Bcl-2 expression, as well as the number of autophagic vesicles in MDA-MB-231 cells. Linc-ROR negatively regulated miR-34a expression by inhibiting histone H3 acetylation in the miR-34a promoter. We conclude that linc-ROR suppresses Gem-induced autophagy and apoptosis in breast cancer cells by silencing miR-34a expression.
Subject(s)
Apoptosis/drug effects , Autophagy/drug effects , Deoxycytidine/analogs & derivatives , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Antimetabolites, Antineoplastic/pharmacology , Apoptosis/genetics , Autophagy/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/genetics , Deoxycytidine/pharmacology , Gene Knockdown Techniques , Histones/metabolism , Humans , Methylation , Promoter Regions, Genetic/genetics , GemcitabineABSTRACT
Resistance to single or multiple chemotherapeutic drugs is a major obstacle in breast cancer therapy. Recent studies have suggested that GPR30 is implicated in mediating cancer cell proliferation. The aim of this study was to examine the anti-tumor effects of the GPR30 antagonist G15 in breast cancer. We found that low concentrations of G15 had little effect on breast cancer cell viability, but could enhance doxorubicin sensitivity in MDA-MB-231 and MCF-7 cells with epithelial phenotypes. In addition, G15 prevented epithelial breast cancer cells undergoing epithelial-mesenchymal transition (EMT) after doxorubicin induction. Moreover, downregulation of GPR30 suppressed the EMT in breast cancer cells. These results support that G15 enhanced doxorubicin sensitivity and prevented the EMT in epithelial breast cancer cells by inhibiting GPR30 expression.
ABSTRACT
BACKGROUND: Annular pancreas in adults is a rare embryologic abnormality detected after development of complications. Embryology, diagnosis and treatment strategies for symptomatic adult annular pancreas remain controversial. In this paper we reevaluated these problems in view of the technological and theoretical advances. METHODS: In 2 patients with annular pancreas, one(36-year-old male patient) presenting with duodenal obstruction and duodenal ulcer associated with duodenocolic fistula underwent Billroth II gastrectomy and fistula ectomy and the other(17-year-old male patient) presenting with duodenal obstruction and duodenal ulcer underwent Billroth II gastrectomy. English language literature about annular pancreas etiology, diagnosis and treatment was reviewed. RESULTS: Both of the patients had uneventfully recovered. Abdominal computed tomography, endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography showed typical images of annular pancreas. Duodenal bypass procedure, choledochojejunostomy, endoscopic sphincterotomy or biliary stenting, and pancreatic resection were alternative to treat this sort of anomaly. CONCLUSIONS: Annular pancreas in adults is a rare congenital abnormality, while newer imaging modalities and an index of suspicion may assist in finding more cases. The management of this congenital anomaly should be individualized according to the associated complications.
